WO2001079562A1 - Aptamer based two-site binding assay - Google Patents

Aptamer based two-site binding assay Download PDF

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Publication number
WO2001079562A1
WO2001079562A1 PCT/US2001/012614 US0112614W WO0179562A1 WO 2001079562 A1 WO2001079562 A1 WO 2001079562A1 US 0112614 W US0112614 W US 0112614W WO 0179562 A1 WO0179562 A1 WO 0179562A1
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WIPO (PCT)
Prior art keywords
molecule
target
capture
reporter
nucleic acid
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Application number
PCT/US2001/012614
Other languages
French (fr)
Inventor
Yun Lin
Jim Heil
Sumedha Jayasena
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Gilead Sciences, Inc.
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Publication date
Application filed by Gilead Sciences, Inc. filed Critical Gilead Sciences, Inc.
Priority to AU2001257091A priority Critical patent/AU2001257091A1/en
Publication of WO2001079562A1 publication Critical patent/WO2001079562A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/56Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6804Nucleic acid analysis using immunogens
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/86Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/7056Selectin superfamily, e.g. LAM-1, GlyCAM, ELAM-1, PADGEM
    • G01N2333/70564Selectins, e.g. CD62
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/914Hydrolases (3)
    • G01N2333/948Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/974Thrombin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Pathology (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

This invention discloses a novel aptamer based two-site binding sandwich assay, employing nucleic acid ligands as capture and/or reporter molecules.

Claims

34 Claims
1. A method for detecting the presence of a target compound in a substance which may contain said target compound comprising: a) exposing a substance which may contain said target compound to a capture molecule capable of binding to said target molecule, wherein said capture molecule is immobilized on a solid support; b) removing the remainder of said substance from said capture molecule:target molecule complex; c) adding to said capture molecule:target molecule complex a reporter molecule capable of binding to said target molecule; and d) detecting said capture molecule:target molecule:reporter molecule complex; wherein said capture molecule, said reporter molecule or both are a nucleic acid ligand to said target molecule.
2. The method of claim 1 wherein said reporter molecule comprises a detection system.
3. The method of claim 2 wherein said detection system is a nucleic acid ligand labeled with a fluorophore.
4. The method of claim 3 wherein said fluorophore is selected from fluorescein or Alexa.
5. The method of claim 1 wherein said solid support is selected from a microsphere particle or a membrane.
6. The method of claim 1 wherein said target molecule is a protein.
7. The method of claim 6 wherein said protein is selected from thrombin or L-
Selectin. 35
8. The method of claim 1 wherein said capture molecule and reporter molecule are nucleic acid ligands.
9. The method of claim 1 wherein said capture molecule is a nucleic acid ligand and said reporter molecule is a protein.
10. The method of claim 1 wherein said capture molecule and reporter molecules bind to separate non-overlapping sites on said target molecule.
11. The method of claim 1 wherein said reporter molecule binds to a site on said capture molecule:target complex.
12. The method of claim 1 wherein said substance is a biological fluid.
13. The method of claim 12 wherein said biological fluid is selected from plasma or urine.
14. The method of claim 1 wherein said detection is achieved by flow cytometry.
15. A method for detecting the presence of a target compound in a substance which may contain said target compound comprising: a) identifying a nucleic acid ligand from a candidate mixture of nucleic acids, said nucleic acid ligand being a ligand of said target compound, by the method comprising: i) contacting the candidate mixture with said target compound, wherein nucleic acids having an increased affinity to said target relative to the candidate mixture may be partitioned from the remainder of the candidate mixture; ii) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; iii) amplifying the increased affinity nucleic acids to yield a ligand- enriched mixture of nucleic acids; and iv) identifying said nucleic acid ligand; 36 b) exposing a substance which may contain said target compound to a capture molecule capable of binding to said target molecule, wherein said capture molecule is immobilized on a solid support; c) removing the remainder of said substance from said capture molecule:target molecule complex; d) adding to said capture molecule:target molecule complex a reporter molecule capable of binding to said target molecule; and e) detecting said capture molecule:target molecule:reporter molecule complex; wherein said capture molecule, said reporter molecule are a nucleic acid ligand to said target molecule identified by the method of step (a).
16. The method of claim 15 wherein said reporter molecule comprises a detection system.
17. The method of claim 16 wherein said detection system is a nucleic acid ligand labeled with a fluorophore.
18. The method of claim 17 wherein said fluorophore is selected from fluorescein or Alexa.
19. The method of claim 15 wherein said solid support is selected from a microsphere particle or a membrane.
20. The method of claim 15 wherein said target molecule is a protein.
21. The method of claim 20 wherein said protein is selected from thrombin or L-Selectin.
22. The method of claim 15 wherein said capture molecule and reporter molecule are nucleic acid ligands. 37
23. The method of claim 15 wherein said capture molecule is a nucleic acid ligand and said reporter molecule is a protein.
24. The method of claim 15 wherein said capture molecule and reporter molecules bind to separate non-overlapping sites on said target molecule.
25. The method of claim 15 wherein said reporter molecule binds to a site on said capture molecule:target complex.
26. The method of claim 15 wherein said substance is a biological fluid.
27. The method of claim 26 wherein said biological fluid is selected from plasma or urine.
28. The method of claim 15 wherein said detection is achieved by flow cytometry.
29. A method for detecting the presence of two or more target compounds in a substance which may contain said target compounds comprising: a) exposing a substance which may contain said target compounds to capture molecules, wherein each capture molecule is capable of binding specifically to a corresponding target compound, wherein said capture molecules are immobilized on a solid support; b) removing the remainder of said substance from said capture molecule:target molecule complexes; c) adding to said capture molecule:target molecule complexes reporter molecules; wherein each reporter molecule is capable of binding specifically to a corresponding target molecule; and d) detecting said capture molecule:target molecule:reporter molecule complexes; wherein said capture molecules, said reporter molecules or both are a nucleic acid ligand to said target molecules.
PCT/US2001/012614 2000-04-18 2001-04-18 Aptamer based two-site binding assay WO2001079562A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001257091A AU2001257091A1 (en) 2000-04-18 2001-04-18 Aptamer based two-site binding assay

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19801600P 2000-04-18 2000-04-18
US60/198,016 2000-04-18

Publications (1)

Publication Number Publication Date
WO2001079562A1 true WO2001079562A1 (en) 2001-10-25

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US (1) US20020037506A1 (en)
AU (1) AU2001257091A1 (en)
WO (1) WO2001079562A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005036171A1 (en) * 2003-10-09 2005-04-21 Koninklijke Philips Electronics N.V. Method and system for detection of a target analyte
EP2386862A1 (en) 2002-10-09 2011-11-16 DMI Biosciences, Inc. Methods and kits for diagnosing appendicitis
WO2012004790A2 (en) 2010-07-06 2012-01-12 Aptateck Bio Ltd. Nucleic acid aptamer-based diagnostic methods with novel techniques for signal enhancement

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6242246B1 (en) * 1997-12-15 2001-06-05 Somalogic, Inc. Nucleic acid ligand diagnostic Biochip
US20070166741A1 (en) * 1998-12-14 2007-07-19 Somalogic, Incorporated Multiplexed analyses of test samples
US6858390B2 (en) * 1998-12-31 2005-02-22 Ingeneus Corporation Aptamers containing sequences of nucleic acid or nucleic acid analogues bound homologously, or in novel complexes
AU2003217379A1 (en) * 2002-02-15 2003-09-09 Somalogic, Inc. Methods and reagents for detecting target binding by nucleic acid ligands
US20030219801A1 (en) * 2002-03-06 2003-11-27 Affymetrix, Inc. Aptamer base technique for ligand identification
AU2003230509B2 (en) * 2002-04-29 2009-03-12 Affibody Ab Sandwich assay and kit
JP2005527220A (en) * 2002-05-28 2005-09-15 ユー.エス. ジェノミクス, インコーポレイテッド Method and apparatus using single polymer analysis
US20040053399A1 (en) * 2002-07-17 2004-03-18 Rudolf Gilmanshin Methods and compositions for analyzing polymers using chimeric tags
AU2003254216A1 (en) * 2002-08-02 2004-02-23 Applera Corporation Fluorescence polarization assay
JP4741458B2 (en) * 2003-01-16 2011-08-03 カプロテック・バイオアナリティクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Method for analyzing capture compounds, collections thereof, and proteomes and composite compositions
JP2006520463A (en) * 2003-01-23 2006-09-07 ユー.エス. ジェノミクス, インコーポレイテッド Methods for analyzing polymer populations
US7745607B2 (en) * 2003-03-31 2010-06-29 Mcmaster University Aptamer selection method
US20050250094A1 (en) 2003-05-30 2005-11-10 Nanosphere, Inc. Method for detecting analytes based on evanescent illumination and scatter-based detection of nanoparticle probe complexes
EP1660679B1 (en) * 2003-08-01 2012-11-14 Dynal Biotech Inc. Self-hybridizing multiple target nucleic acid probes and methods of use
US20050112671A1 (en) * 2003-11-07 2005-05-26 U.S. Genomics, Inc. FRET efficiency methods
US20050112585A1 (en) * 2003-11-21 2005-05-26 Dominic Zichi Method for adjusting the quantification range of individual analytes in a multiplexed assay
JP2007525661A (en) * 2003-12-12 2007-09-06 セントルイス ユニバーシティー Biosensors for detection of large molecules and other analytes
JP2007518107A (en) 2004-01-13 2007-07-05 ユー.エス. ジェノミクス, インコーポレイテッド Detection and quantification of analytes in solution using polymers
JP2007529758A (en) * 2004-03-19 2007-10-25 ユー.エス. ジェノミクス, インコーポレイテッド Compositions and methods for single molecule detection
US20060003339A1 (en) * 2004-06-30 2006-01-05 Fuernkranz Hans A Two-hybrid system
US8956857B2 (en) 2005-06-06 2015-02-17 Mediomics, Llc Three-component biosensors for detecting macromolecules and other analytes
US7795009B2 (en) * 2005-06-15 2010-09-14 Saint Louis University Three-component biosensors for detecting macromolecules and other analytes
US8945840B2 (en) * 2005-06-10 2015-02-03 Saint Louis University Methods for the selection of aptamers
US7811809B2 (en) * 2005-06-15 2010-10-12 Saint Louis University Molecular biosensors for use in competition assays
WO2007056250A2 (en) * 2005-11-04 2007-05-18 U.S. Genomics, Inc. Heterogeneous assay of analytes in solution using polymers
EP2952894B1 (en) * 2006-01-17 2017-08-30 Somalogic, Inc. Kits comprising aptamers
WO2007095279A2 (en) * 2006-02-14 2007-08-23 University Of Florida Research Foundation, Inc. Dual nanoparticle assay for detection and separation of biological species
US20110136099A1 (en) 2007-01-16 2011-06-09 Somalogic, Inc. Multiplexed Analyses of Test Samples
WO2008134069A2 (en) * 2007-04-26 2008-11-06 University Of Florida Research Foundation Anchored ligand agents
US20100294665A1 (en) * 2007-07-12 2010-11-25 Richard Allen Method and system for transferring and/or concentrating a sample
US8906700B2 (en) 2007-11-06 2014-12-09 Ambergen, Inc. Methods and compositions for phototransfer
SE533515C2 (en) * 2008-04-16 2010-10-12 Aamic Ab Analysis procedure for simultaneous analysis of several analytes
CA2744003C (en) 2008-11-21 2016-03-15 Mediomics Llc Biosensor for detecting multiple epitopes on a target
WO2010093223A2 (en) * 2009-02-16 2010-08-19 동국대학교산합협력단 Target substance detection method using aptamer
US9329178B2 (en) 2009-02-16 2016-05-03 Dongguk University Industry-Academic Cooperation Foundation Target substance detection method using aptamer
WO2011100561A1 (en) 2010-02-12 2011-08-18 Saint Louis University Molecular biosensors capable of signal amplification
US20150031585A1 (en) * 2011-03-10 2015-01-29 Somalogic, Inc. Multiaptamer Target Detection
US20130183658A1 (en) * 2012-01-16 2013-07-18 Bret T. Barnhizer Methods and Devices for Rapid Detection of Live Microorganisms by Aptamers and/or Antibodies Immobilized on Permeable Membranes
KR102348283B1 (en) * 2013-09-24 2022-01-10 소마로직, 인크. Multiaptamer target detection
WO2016040830A1 (en) 2014-09-12 2016-03-17 Mediomics, Llc Molecular biosensors with a modular design
JP7241619B2 (en) * 2019-06-19 2023-03-17 アークレイ株式会社 Target substance detection method, target substance detection kit, target substance detection system

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5789163A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Enzyme linked oligonucleotide assays (ELONAS)
US5853984A (en) * 1990-06-11 1998-12-29 Nexstar Pharmaceuticals, Inc. Use of nucleic acid ligands in flow cytometry

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US51974A (en) * 1866-01-09 Improvement in trusses
DE229046T1 (en) * 1985-03-30 1987-12-17 Marc Genf/Geneve Ballivet METHOD FOR OBTAINING DNA, RNS, PEPTIDES, POLYPEPTIDES OR PROTEINS BY DNA RECOMBINANT METHOD.
US5459015A (en) * 1990-06-11 1995-10-17 Nexstar Pharmaceuticals, Inc. High-affinity RNA ligands of basic fibroblast growth factor
US6449562B1 (en) * 1996-10-10 2002-09-10 Luminex Corporation Multiplexed analysis of clinical specimens apparatus and method
US6242246B1 (en) * 1997-12-15 2001-06-05 Somalogic, Inc. Nucleic acid ligand diagnostic Biochip
US6180348B1 (en) * 1998-04-20 2001-01-30 Weihua Li Method of isolating target specific oligonucleotide ligands

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5789163A (en) * 1990-06-11 1998-08-04 Nexstar Pharmaceuticals, Inc. Enzyme linked oligonucleotide assays (ELONAS)
US5853984A (en) * 1990-06-11 1998-12-29 Nexstar Pharmaceuticals, Inc. Use of nucleic acid ligands in flow cytometry

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2386862A1 (en) 2002-10-09 2011-11-16 DMI Biosciences, Inc. Methods and kits for diagnosing appendicitis
EP2386864A1 (en) 2002-10-09 2011-11-16 DMI Biosciences, Inc. Diagnosis and monitoring of Ischemia
EP2386863A1 (en) 2002-10-09 2011-11-16 DMI Biosciences, Inc. Diagnosis and monitoring of multiple organ failure
WO2005036171A1 (en) * 2003-10-09 2005-04-21 Koninklijke Philips Electronics N.V. Method and system for detection of a target analyte
WO2012004790A2 (en) 2010-07-06 2012-01-12 Aptateck Bio Ltd. Nucleic acid aptamer-based diagnostic methods with novel techniques for signal enhancement
WO2012004790A3 (en) * 2010-07-06 2012-04-12 Aptateck Bio Ltd. Nucleic acid aptamer-based detection methods characterized by signal enhancement
US9772330B2 (en) 2010-07-06 2017-09-26 Aptateck Bio Ltd. Nucleic acid aptamer-based diagnostic methods with novel techniques for signal enhancement

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AU2001257091A1 (en) 2001-10-30
US20020037506A1 (en) 2002-03-28

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